The objective of the proposed research is to identify and further characterize the biochemical and physiologic pathways that are responsible for the inflammation associated with urticaria, angioedema, urticarial vasculitis, and vasculitis associated with autoimmune disease. We will extend our studies of IgE mediated cold urticaria and distinguish whether an IgE cryoglobulin or an IgE antibody to a cold dependent skin antigen is involved. We will purify the IgE from patients with passively transferrable cold urticaria to study its mechanism of action in greater detail. We will further examine mediator release during exercise challenge of cholinergic urticaria patients and look for evidence of increased release of acetylcholine or increased tissue and cellular responsiveness to acetylcholine as an underlying abnormality in the disease. The status of skin mast cells upon challenge of patients with cold and cholinergic urticaria will be examined. We will seek evidence of kinin release in hereditary angioedema as a result of activation of the classical complement pathway and will purify and characterize any kinin that is found. The potential role of bradykinin as a mediator of the swelling seen in this disease will be clarified. The role of CT INH in controlling the activatability of Hageman factor dependent bradykinin generation will be assessed and an interrelationship between activation of the intrinsic coagulation and classical complement pathways will be sought. The various types of tissue pathology seen in chronic urticaria will be characterized by light and electron microscopy including immunofluorescence and/or immunoperoxidase analyses. The reaction will also be compared with that seen in early and late IgE dependent skin reactions as well as delayed hypersensitivity reactions. The contributions made by histamine, serotonin, kinins and prostaglandins to the inflammatory reaction seen, will be defined.